Bisphosphonate-induced reductions in rat femoral bone energy absorption and toughness are testing rate-dependent

Eric R. Smith, Matthew Allen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Bisphosphonates have been used for years to suppress bone turnover and reduce fracture risk. Bisphosphonates have recently been associated with atypical femoral fractures, which are catastrophic, low trauma, brittle fractures that appear to occur more frequently than in untreated individuals. Previous work using a dog model has demonstrated bisphosphonate-induced reductions in bone toughness (the inverse of brittleness), yet data are lacking to show this occurs in rodents. The goal of this study was to determine if bisphosphonate-induced alterations in toughness could be quantified in rats. At 26 weeks of age, skeletally mature rats (n = 32 total) were given an injection of either zoledronate (100 μg/kg body weight) or vehicle (0.5 ml saline). Five weeks post-injection, both femora were collected and analyzed for geometry and mechanical properties. To assess the effect of testing rate on the biomechanical outcomes, the left femora were broken at 2 mm/min, while the right femora were broken at 20 mm/min. The results showed a significantly lower energy to failure in zoledronate-treated animals compared to vehicle at the slow testing rate (-15%, p < 0.05) with no difference at the faster rate. While there was not a significant interaction between drug and testing rate for toughness to fracture (p = 0.07), toughness between ultimate stress and fracture was significantly lower with zoledronate only at the slow rate (-40%, p < 0.05). These data document that bisphosphonate-induced reductions in energy absorption and toughness can be quantified in rats yet they are highly dependent on testing rate.

Original languageEnglish
Pages (from-to)1317-1322
Number of pages6
JournalJournal of Orthopaedic Research
Volume31
Issue number8
DOIs
StatePublished - Aug 2013

Fingerprint

zoledronic acid
Diphosphonates
Thigh
Bone and Bones
Femur
Stress Fractures
Injections
Femoral Fractures
Bone Remodeling
Drug Interactions
Rodentia
Body Weight
Dogs
Wounds and Injuries

Keywords

  • atypical femoral fractures
  • mechanical testing
  • sub-trochanteric fracture
  • zoledronate

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Bisphosphonate-induced reductions in rat femoral bone energy absorption and toughness are testing rate-dependent. / Smith, Eric R.; Allen, Matthew.

In: Journal of Orthopaedic Research, Vol. 31, No. 8, 08.2013, p. 1317-1322.

Research output: Contribution to journalArticle

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abstract = "Bisphosphonates have been used for years to suppress bone turnover and reduce fracture risk. Bisphosphonates have recently been associated with atypical femoral fractures, which are catastrophic, low trauma, brittle fractures that appear to occur more frequently than in untreated individuals. Previous work using a dog model has demonstrated bisphosphonate-induced reductions in bone toughness (the inverse of brittleness), yet data are lacking to show this occurs in rodents. The goal of this study was to determine if bisphosphonate-induced alterations in toughness could be quantified in rats. At 26 weeks of age, skeletally mature rats (n = 32 total) were given an injection of either zoledronate (100 μg/kg body weight) or vehicle (0.5 ml saline). Five weeks post-injection, both femora were collected and analyzed for geometry and mechanical properties. To assess the effect of testing rate on the biomechanical outcomes, the left femora were broken at 2 mm/min, while the right femora were broken at 20 mm/min. The results showed a significantly lower energy to failure in zoledronate-treated animals compared to vehicle at the slow testing rate (-15{\%}, p < 0.05) with no difference at the faster rate. While there was not a significant interaction between drug and testing rate for toughness to fracture (p = 0.07), toughness between ultimate stress and fracture was significantly lower with zoledronate only at the slow rate (-40{\%}, p < 0.05). These data document that bisphosphonate-induced reductions in energy absorption and toughness can be quantified in rats yet they are highly dependent on testing rate.",
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